Stabilization of invariant chain mRNA by 12-O-tetradecanoylphorbol-13-acetate is blocked by IFN-gamma in a murine B lymphoma cell line.
Activation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate (TPA) increased steady-state levels of mRNA encoding the major histocompatibility complex (MHC) class II antigen I-A beta and the class II antigen-associated invariant chain (Ii, CD74) in A20 B lymphoma cells and in normal mouse B cells. The increase in Ii mRNA levels appeared to be due to a slight increase in the rate of gene transcription and an increase in the stability of Ii mRNA. The half-life of Ii mRNA increased from 12 h to >24 h following treatment with TPA, as determined by Northern blot analysis following actinomycin D treatment or by the [3H]-uridine pulse-chase method. Interferon-gamma (IFN-gamma), which has been well characterized as a cytokine that induces class II antigens and the Ii, increased Ii expression slightly in A20 cells. However, cotreatment of cells with TPA and IFN-gamma resulted in a block in the TPA-induced increase in Ii expression. Transcription of the Ii gene was minimally affected following treatment with IFN-gamma alone, and cells treated with both TPA and IFN-gamma had the same transcription rate as the control cells. IFN-gamma did, however, block stabilization of Ii mRNA by TPA. Activation of PKC by TPA, which was previously shown to lead to membrane translocation and downregulation, was not inhibited by IFN-gamma. Therefore, IFN-gamma appeared to block a downstream signal transduction pathway activated by PKC that controls stability of Ii mRNA.
Shih
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Department of Biology, Arizona State University, Tempe 85287-1501, USA.
Soesilo
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Floyd-Smith
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D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004789:Enzyme Activation; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007371:Interferon-gamma / Q000627:therapeutic use*; D007527:Isoenzymes / Q000187:drug effects; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000949:Histocompatibility Antigens Class II; D007527:Isoenzymes; D012333:RNA, Messenger; C045084:invariant chain; D007371:Interferon-gamma; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate